The proposed study is designed to characterize pulmonary pathophysiological alterations induced by IgE and to elucidate the mechanism(s) by which such alterations occur. The experimental design involves the utilization of a unique model system in which rabbits sensitized to horseradish peroxidase (HRP) synthesize only IgE antibody to that antigen and upon intravenous challenge exhibit systemic anaphylaxis--an explosive short-term reaction which is generally fatal in less than five minutes if the challenging antigen dose is 5 mg HRP. This systemic allergic reaction is in the process of being characterized by simultaneously monitoring the respiratory and hemodynamic changes in function so as to determine the sequence of events resulting from the IgE-induced assault on the organism as a whole. Preliminary results indicate severe effects in both cardiovascular and respiratory function. It is proposed that this system be studied with lower doses of challenging antigen known to yield IgE induced pulmonary changes of a milder nature to determine if repeated challenge over several weeks will result in pathology of a subacute or chronic nature. In other studies of this IgE-induced systemic reaction, aerosol vs. intravenous administration of antigen will be compared for differences with respect to the pattern of physiologic alterations. The presence of administered anti-HRP IgG antibody will be examined as to effects on this reaction. Histologic examinations will be performed to determine the relative numbers and distribution of mast cells and amount of histamine in the lungs of sensitized and nonsensitized rabbits. The extent of degranulation of mast cells and the localization of antigen associated with the various experimental modifications of the IgE induced systemic reaction will be examined in order to assess the involvement of local lung tissue mediator release occurring as a result of antigen interaction with mast-cell- bound IgE antibody.